# Neuropeptide W

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{{Short description|Mammalian protein found in Homo sapiens}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{infobox protein
| image=Neuropeptide W primary sequence.png
| caption=Neuropeptide W primary sequence using three letters code. N-terminal represented in blue. C-terminal represented in red.
| Wikidata =Q21173201
| UniProt =Q8N729
}}
'''Neuropeptide W''' or '''preprotein L8''' is a short human [neuropeptide](/source/neuropeptide).<ref name="Takenoya_2012">{{cite journal | vauthors = Takenoya F, Kageyama H, Hirako S, Ota E, Wada N, Ryushi T, Shioda S | title = Neuropeptide W | journal = Frontiers in Endocrinology | volume = 3 | pages = 171 | date = December 2012 | pmid = 23267349 | pmc = 3527818 | doi = 10.3389/fendo.2012.00171 | doi-access = free }}</ref> Neuropeptide W acts as a [ligand](/source/ligand) for two [neuropeptide B/W receptors](/source/Neuropeptide_B%2FW_receptor), [NPBWR1](/source/NPBWR1) and [NPBWR2](/source/NPBWR2), which are integrated in [GPCR](/source/GPCR)s family of [alpha-helical](/source/alpha-helical) [transmembrane protein](/source/transmembrane_protein)s.<ref>{{Cite web | title = Neuropeptide W/neuropeptide B receptors {{!}} G protein-coupled receptors {{!}} IUPHAR/BPS Guide to PHARMACOLOGY|url=https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=45|access-date=2020-11-08|website=www.guidetopharmacology.org}}</ref><ref>{{cite journal | vauthors = Zhang Y, Wang Z, Parks GS, Civelli O | title = Novel neuropeptides as ligands of orphan G protein-coupled receptors | journal = Current Pharmaceutical Design | volume = 17 | issue = 25 | pages = 2626–2631 | date = 2011 | pmid = 21728976 | pmc = 5828022 | doi = 10.2174/138161211797416110 }}</ref>

== Structure ==
There are two forms of neuropeptide W whose precursor is encoded by [NPW](/source/NPW) gene.<ref>{{Cite web | vauthors = Chen C, Huang H, Wu C | title = UniProtKB - Q8N729 (NPW_HUMAN) | date = July 23, 2020 | url = https://www.uniprot.org/uniprot/Q8N729 | access-date = 26 October 2020 | website = Protein Bioinformatics Databases and Resources }}</ref>

The 23-amino-acid form (neuropeptide W-23) is the one that activates the receptors whereas the C-terminally extended form (neuropeptide W-30) is less effective. These isoforms were demonstrated in different species like rat, human, chicken, mouse and pig.<ref>{{Cite web | title = Neuropeptide W/neuropeptide B receptors {{!}} G protein-coupled receptors {{!}} IUPHAR/BPS Guide to PHARMACOLOGY|url=https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=45|access-date=2020-11-08|website=www.guidetopharmacology.org}}</ref>

The name of neuropeptide W is due to the tryptophan residues located on both sides, the N- side and -C side, in its two mature forms. 

== Location==
Neuropeptide W was first identified in porcine [hypothalamus](/source/hypothalamus) in 2002.<ref>{{cite journal | vauthors = Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y, Abe M, Watanabe T, Asami T, Kitada C, Mori M, Onda H, Fujino M | title = Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 39 | pages = 35826–35832 | date = September 2002 | pmid = 12130646 | doi = 10.1074/jbc.M205337200 | doi-access = free }}</ref> In humans, it is highly confined in neurons of the [substantia nigra](/source/substantia_nigra) and the [spinal cord](/source/spinal_cord), and fewer expressed in neurons of the [hippocampus](/source/hippocampus), hypothalamus, [amygdala](/source/amygdala), parietal cortex and cerebellum. <ref>{{cite journal | vauthors = Takenoya F, Kageyama H, Shiba K, Date Y, Nakazato M, Shioda S | title = Neuropeptide W: a key player in the homeostatic regulation of feeding and energy metabolism? | journal = Annals of the New York Academy of Sciences | volume = 1200 | issue = 1 | pages = 162–169 | date = July 2010 | pmid = 20633144 | doi = 10.1111/j.1749-6632.2010.05642.x | bibcode = 2010NYASA1200..162T | s2cid = 205934962 }}</ref> It can also be found in some peripheral tissues such as trachea, stomach, liver, kidney prostate, uterus and ovary. It has to be said that tissue distribution information is still lacking.<ref>{{cite journal | vauthors = Brezillon S, Lannoy V, Franssen JD, Le Poul E, Dupriez V, Lucchetti J, Detheux M, Parmentier M | title = Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 2 | pages = 776–783 | date = January 2003 | pmid = 12401809 | doi = 10.1074/jbc.M206396200 | doi-access = free }}</ref> For the moment, Neuropeptide W location differences between studied species (rat, mouse, chicken, pig) are slight, even though quantities differ between the organs.<ref name="Dvorakova_2018">{{cite journal | vauthors = Dvorakova MC | title = Distribution and Function of Neuropeptides W/B Signaling System | journal = Frontiers in Physiology | volume = 9 | article-number = 981 | date = 2018-07-24 | pmid = 30087623 | pmc = 6067035 | doi = 10.3389/fphys.2018.00981 | doi-access = free }}</ref>

== Function ==

=== Neuropeptide W in CNS ===
Neuropeptide W in the [central nervous system](/source/central_nervous_system) is implicated in feeding activity and energy metabolism, in the adrenal axis stress response, and the regulation of neuroendocrine functions like hormone release from the [pituitary gland](/source/pituitary_gland), but it is not considered as an inhibitory or regulatory factor in it. Neuropeptide W may also be involved in autonomic regulation, pain sensation, emotions, anxiety and fear.<ref>{{cite journal | vauthors = Taylor MM, Yuill EA, Baker JR, Ferri CC, Ferguson AV, Samson WK | title = Actions of neuropeptide W in paraventricular hypothalamus: implications for the control of stress hormone secretion | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 288 | issue = 1 | pages = R270–R275 | date = January 2005 | pmid = 15345475 | doi = 10.1152/ajpregu.00396.2004 }}</ref><ref>{{cite journal | vauthors = Baker JR, Cardinal K, Bober C, Taylor MM, Samson WK | title = Neuropeptide W acts in brain to control prolactin, corticosterone, and growth hormone release | journal = Endocrinology | volume = 144 | issue = 7 | pages = 2816–2821 | date = July 2003 | pmid = 12810535 | doi = 10.1210/en.2002-0161 | doi-access = free }}</ref> Neuropeptide W has been shown to have [analgesic](/source/analgesic) and [anticonvulsant](/source/anticonvulsant) effects, suggesting that its receptors may have useful medical applications.<ref name="Green_2011">{{cite journal | vauthors = Green BR, Smith M, White KL, White HS, Bulaj G | title = Analgesic neuropeptide W suppresses seizures in the brain revealed by rational repositioning and peptide engineering | journal = ACS Chemical Neuroscience | volume = 2 | issue = 1 | pages = 51–56 | date = January 2011 | pmid = 22826747 | pmc = 3400287 | doi = 10.1021/cn1000974 }}</ref>

It seems that regulation of feeding behaviour and energy [metabolism](/source/metabolism) is the primary function of the neuropeptide W signaling system.<ref name="Parker_2012">{{cite journal | vauthors = Parker JA, Bloom SR | title = Hypothalamic neuropeptides and the regulation of appetite | journal = Neuropharmacology | volume = 63 | issue = 1 | pages = 18–30 | date = July 2012 | pmid = 22369786 | doi = 10.1016/j.neuropharm.2012.02.004 }}</ref><ref name="Li_2018">{{cite journal | vauthors = Li H, Kentish SJ, Wittert GA, Page AJ | title = The role of neuropeptide W in energy homeostasis | journal = Acta Physiologica | location = Oxford, England | volume = 222 | issue = 1 | date = January 2018 | article-number = e12884 | pmid = 28376284 | doi = 10.1111/apha.12884 }}</ref> On the one hand, Neuropeptide W regulates the endocrine signals aimed at anterior hypophysis. This stimulates both the need for water (thirst) and the need for food (hunger). On the other hand, it plays a compensatory role in energy metabolism.<ref>{{cite journal | vauthors = Mondal MS, Yamaguchi H, Date Y, Shimbara T, Toshinai K, Shimomura Y, Mori M, Nakazato M | title = A role for neuropeptide W in the regulation of feeding behavior | journal = Endocrinology | volume = 144 | issue = 11 | pages = 4729–4733 | date = November 2003 | pmid = 12959997 | doi = 10.1210/en.2003-0536 | doi-access = free }}</ref>

Regarding the adrenal axis response to stress, it plays a relevant role as a messenger in brain networks that help the activation of HPA ([hypothalamic–pituitary–adrenal axis](/source/hypothalamic%E2%80%93pituitary%E2%80%93adrenal_axis)), which will cause the response to stress.<ref name="Dvorakova_2018" />

An example of neuroendocrine functions is the regulation of the secretion of [cortisol](/source/cortisol) due to the activation or deactivation of neuropeptide B/W receptors.<ref>{{cite journal | vauthors = Mazzocchi G, Rebuffat P, Ziolkowska A, Rossi GP, Malendowicz LK, Nussdorfer GG | title = G protein receptors 7 and 8 are expressed in human adrenocortical cells, and their endogenous ligands neuropeptides B and w enhance cortisol secretion by activating adenylate cyclase- and phospholipase C-dependent signaling cascades | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 90 | issue = 6 | pages = 3466–3471 | date = June 2005 | pmid = 15797961 | doi = 10.1210/jc.2004-2132 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Singh G, Davenport AP | title = Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system | journal = British Journal of Pharmacology | volume = 148 | issue = 8 | pages = 1033–1041 | date = August 2006 | pmid = 16847439 | pmc = 1752024 | doi = 10.1038/sj.bjp.0706825 }}</ref>

Moreover, Neuropeptide W  is found in an area that is connected with preauthonomic centers in the brainstem and spinal cord. Because of this location, there is a chance that it can affect some cardiovascular function.<ref>{{cite journal | vauthors = Pate AT, Yosten GL, Samson WK | title = Neuropeptide W increases mean arterial pressure as a result of behavioral arousal | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 305 | issue = 7 | pages = R804–R810 | date = October 2013 | pmid = 23926134 | pmc = 3798801 | doi = 10.1152/ajpregu.00119.2013 }}</ref>

Infusion of neuropeptide W has been shown to suppress the eating of food and body weight and increase heat production and body temperature, this verifies its works as an endogenous catabolic [signaling molecule](/source/signaling_molecule).<ref name="Takenoya_2012" />

=== Neuropeptide W in peripheral tissues ===
While the central roles of neuropeptide W are better studied, it is also important in peripheral tissues in functions such as regulation of vascular muscle tone, regulation of gastric tension sensitive vagus nerve signalling, and [insulin](/source/insulin) secretion.<ref name="Chottova_Dvorakova_2018">{{cite journal | vauthors = Chottova Dvorakova M | title = Distribution and Function of Neuropeptides W/B Signaling System | journal = Frontiers in Physiology | volume = 9 | article-number = 981 | date = 2018 | pmid = 30087623 | pmc = 6067035 | doi = 10.3389/fphys.2018.00981 | doi-access = free }}</ref>

== See also ==
* [Neuropeptide B](/source/Neuropeptide_B)
* [Neuropeptide FF](/source/Neuropeptide_FF)

== References ==
{{Reflist}}

Category:Neuropeptides
Category:G proteins
Category:Genes on human chromosome 17

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Adapted from the Wikipedia article [Neuropeptide W](https://en.wikipedia.org/wiki/Neuropeptide_W) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Neuropeptide_W?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.